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Frontiers of Medicine >> 2021, Volume 15, Issue 4 doi: 10.1007/s11684-020-0780-y

Targeting “undruggable” c-Myc protein by synthetic lethality

. Division of Genome Medicine and Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;.. Institute of Genetics, Zhejiang University and Department of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China;.. Zhejiang Laboratory for Systems & Precision Medicine, Zhejiang University Medical Center, Hangzhou 311121, China

Received: 2020-12-31 Accepted: 2021-03-05 Available online: 2021-03-05

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Abstract

Synthetic lethal screening, which exploits the combination of mutations that result in cell death, is a promising method for identifying novel drug targets. This method provides a new avenue for targeting “undruggable” proteins, such as c-Myc. Here, we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network, whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells. We further discuss strategies to identify these functional nodes in the context of synthetic lethality. We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

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